A team of NIH-funded researchers has successfully regenerated rabbit
joints using a cutting edge process to form the joint inside the body,
or in vivo. Regenerative in vivo procedures are performed by stimulating
previously irreparable organs or tissues to heal themselves. In this
study, bioscaffolds, or three-dimensional structures made of biocompatible
and biodegradable materials in the shape of the tissue, were infused
with a protein to promote growth of the rabbit joint.

The experiment demonstrated the feasibility of an approach to growing
dissimilar tissues, such as cartilage and bone, derived entirely from
the host’s own cells. Results of the study are in the July 29 issue of
The Lancet.

Regeneration activity relied on the host's supply of cells to the joint,
local tissue response, and functional stimulation to recreate the entire
surface of the joint cartilage together with the bone. The approach sidesteps
problems encountered in transplantation of cells grown ex vivo, such
as immunological rejection, pathogen transmission, and potential formation
of tumors.

The research team laser-scanned the surface contours of a rabbit forelimb
joint and made a 3-D model that was used to create an anatomically dimensioned
bioscaffold. Some rabbits in the study received a bioscaffold infused
with a collagen gel loaded with the protein, called transforming growth
factor beta 3 (TGFB3), while other rabbits received bioscaffolds without
TGFB3.

Bioscaffolds infused with TGFB3 recruited 130 percent more cells and
grew a whole layer of cartilage tissue with greater compressive and shear
properties than those who received the bioscaffold without the TGFB3.
Rabbits with TGFB3-infused bioscaffolds resumed weight-bearing activity
and locomotion three to four weeks after joint replacement. At five to
eight weeks after surgery, these rabbits moved nearly as well as the
control rabbits. By contrast, rabbits whose bioscaffolds did not contain
TGFB3 continued to limp.

The research team included Chang H. Lee, Avital Mendelson, Eduardo K.
Moioli, and Jeremy J. Mao of Columbia University Medical Center Tissue
Engineering and Regenerative Medicine Laboratory, New York City; James
L. Cook, University of Missouri School of Veterinary Medicine, Columbia;
and Hai Yao, Clemson University and Medical University of South Carolina
Department of Bioengineering, Charleston.

"Cartilage is one of the most resistant tissues for regeneration.
This is the first time an entire cartilage joint was regenerated. By
successfully regenerating cartilage in this way, we hope that this approach
would work with other tissues without cell transplantation," Dr.
Mao said.

Future work could replace arthritic joints in pre-clinical animal models
and ultimately in arthritis patients who need total joint replacement.

Osteoarthritis is the world's leading cause of chronic disabilities.
The disease involves structural breakdown of cartilage and bone, and
affects approximately 80 million people in the United States.

"The aging population with arthritis is expected to double by 2030,
when the last of the baby boomers become seniors," adds Dr. Mao.
Current joint replacements have only a 10–15 year lifespan which may
not be long enough for the increasing numbers of arthritis patients who
are 65 years old or younger.

"The potential for in vivo tissue regeneration is enormous," says
Dr. Christine Kelley, director of the NIBIB Division of Discovery Science
and Technology. "Dr. Mao's work with repairing damaged bone and
cartilage by recruiting host cells within a living animal could help
pave the way for advanced treatment of arthritis and other diseases in
humans."

This work was supported by grants from the National Institute of Biomedical
Imaging and Bioengineering (NIBIB) (National Institutes of Health grant
R01EB002332) and New York State Stem Cell Science.

NIBIB, a component of NIH, is dedicated to improving health by bridging
the physical and biological sciences to develop and apply new biomedical
technologies. Additional information and publications are available at http://www.nibib.nih.gov.

About the National Institutes of Health (NIH): NIH, the nation's medical research agency, includes 27 Institutes and Centers
and is a component of the U.S. Department of Health and Human Services. NIH
is the primary federal agency conducting and supporting basic, clinical, and
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and cures for both common and rare diseases. For more information about NIH
and its programs, visit http://www.nih.gov.